Monocytes/macrophages and granulocytes develop through an ordery, multipstep process of differentiation from rare pluripotent stem cells in the bone marrow. This differentiation is characterized not only by changes in the morphology and histochemistry of cells, but also by changes in the expression of cell surface structures. Some of these molecules are presumably involved in performing specific effector functions while others may be important for directing the process of differentiation. The structure of several human monocyte/macrophage and granulocyte differentiation antigens wil be analyzed by determining the predicted protein sequences from cDNA clones encoding these molecules. These cDNA clones will be isolated using probes obtained from L cells which have been transformed with high molecular weight DNA and express the molecules of interest on the cell surface. These reagents will allow us to compare the structures of these molecules to each other and to other known differentiation antifens. They will also allow us to examine whether these molecules are members of multigene families and to determine if similarly expressed molecules are encoded by genes located on the same or different chromosomes. Ultimately, we will study the regulation of expression and function of these differentiation molecules at the molecular level.